The Effect of Probiotics (VSL) on Portal Hypertension

Portal Hypertension Clinical Trial

Official title:

A Randomized Controlled Trial on the Beneficial Effects of Probiotics on Portal Hemodynamics in Decompensated Cirrhotic Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01032941
• Other study ID #: VSL3PHTNUoA
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: December 3, 2009
• Last updated: January 18, 2012
• Start date: December 2009
• Est. completion date: June 2011

Study information

• Verified date: January 2012
• Source: University of Alberta
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical Trial Summary

The investigators will address the hypothesis that portal hypertension is mediated in part by bacterial or endotoxin translocation and the production of inflammatory mediators (tumor necrosis factor-α (TNFα), etc.). The investigators hypothesize that food supplementation with the probiotic product VSL#3 in patients with Child Pugh B/C cirrhosis will have a beneficial effect on in portal pressure (as measured by the HVPG) by reducing inflammatory mediators and improving systemic and splanchnic hemodynamics.

Description:

We have recently completed an open-label uncontrolled trial of the probiotic VSL#3 in 8 patients with compensated cirrhosis and evidence of portal hypertension (VIP study) to determine whether this agent would have beneficial effects in portal pressure reduction (unpublished data Tandon, P. et al.). The open label design and the inclusion of compensated (Child Pugh A) cirrhotic patients in this initial study were chosen to confirm the safety and tolerance of VSL#3 and the safety of the portal pressure measurements at our center. No changes of physical status occured. There was a non-significant reduction in portal pressure from 19.7 to 18.1 mm Hg after 2 months of VSL#3 supplementation. Furthermore, there was a significant reduction in the serum aldosterone level (p=0.03). IL-8 levels were reduced in 4/6 patients analyzed to date. These results suggest that VSL#3 results in cytokine reduction and an improvement in the effective circulating volume even in these well-compensated cirrhotic patients. The comparison of the rest of the pro-inflammatory mediators and stool microflora is still being analyzed.

The data in our initial study is very promising. As our patients were compensated cirrhotics with normal intestinal permeability and only mild baseline perturbations in hepatic function parameters (INR, bilirubin, albumin) and neurohormonal markers (aldosterone, renin), it is not surprising that a reduction in portal pressure was not identified. Consistent with previous studies however, these local results confirm the safety and tolerance of both VSL#3 as well as portal pressure measurements in cirrhotic patients (20,24,25).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: June 2011
• Est. primary completion date: June 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Age 18-80

• Cirrhosis

• Childs-Pugh Class B/C

Exclusion Criteria:

• Bacterial infection

• Grade 3-4 hepatic encephalopathy

• GI bleeding in the past 2 weeks

• Hepatocellular carcinoma beyond the Milan criteria

• Transjugular intrahepatic portosystemic shunt (TIPS), surgical shunt

• Portal vein thrombosis

• Antibiotics in the past 2 weeks

• Myocardial infarction, stroke or life-threatening arrhythmia within the last 6 months

• Active alcohol or illicit drug use

• Failure to consent to the study

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Health Services Research

Related Conditions & MeSH terms

• Hypertension
• Hypertension, Portal
• Portal Hypertension

Intervention

Drug:
• Probiotic
Patients in this group will be given the probiotic VSL#3 2 packets BID for a total of 8 weeks.

Locations

Country	Name	City	State
Canada	University of Alberta	Edmonton	Alberta

Sponsors (1)

Lead Sponsor	Collaborator
University of Alberta

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Reduction in portal pressure		12 months	No